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https://www.readbyqxmd.com/read/28813752/atypical-presentations-of-tularemia
#1
Karah Odegaard, Beth Boersma, James Keegan
Francisella tularensis is a gram-negative coccobacillus that causes a condition commonly referred to as tularemia. There has been a dramatic increase in tularemia cases reported in South Dakota, many of which were challenging to diagnose due to atypical clinical manifestations. We describe an interesting case of pneumonic tularemia and summarize six similar cases, several of which presented with lung nodules suggestive of malignancy. According to the literature, this is only the third outbreak of pneumonic tularemia reported in the U...
May 2017: South Dakota Medicine: the Journal of the South Dakota State Medical Association
https://www.readbyqxmd.com/read/28807561/mass-spectrometry-analysis-of-intact-francisella-bacteria-identifies-lipid-a-structure-remodeling-in-response-to-acidic-ph-stress
#2
Camille B Robert, Michael Thomson, Alain Vercellone, Francesca Gardner, Robert K Ernst, Gérald Larrouy-Maumus, Jérôme Nigou
Structural modification of lipid A, the lipid anchor of LPS, is one of the strategies used by Gram-negative bacteria to evade host innate immunity. Francisella tularensis is a human pathogen that infects and replicates within phagocytic cells. It produces an atypical lipid A, whose structure precludes an efficient recognition by both innate immune players, TLR4 and cationic antimicrobial peptides. Interestingly, a recent report indicates that the lipid A of Francisella (LVS vaccinal strain) undergoes polar modifications when bacteria are grown in human macrophages as compared to in broth...
August 11, 2017: Biochimie
https://www.readbyqxmd.com/read/28791299/differential-microrna-analyses-of-burkholderia-pseudomallei-and-francisella-tularensis-exposed-hpbmcs-reveal-potential-biomarkers
#3
Regina Z Cer, J Enrique Herrera-Galeano, Kenneth G Frey, Kevin L Schully, Truong V Luu, John Pesce, Vishwesh P Mokashi, Andrea M Keane-Myers, Kimberly A Bishop-Lilly
Increasing evidence that microRNAs (miRNAs) play important roles in the immune response against infectious agents suggests that miRNA might be exploitable as signatures of exposure to specific infectious agents. In order to identify potential early miRNA biomarkers of bacterial infections, human peripheral blood mononuclear cells (hPBMCs) were exposed to two select agents, Burkholderia pseudomallei K96243 and Francisella tularensis SHU S4, as well as to the nonpathogenic control Escherichia coli DH5α. RNA samples were harvested at three early time points, 30, 60, and 120 minutes postexposure, then sequenced...
2017: International Journal of Genomics
https://www.readbyqxmd.com/read/28774562/defective-anti-polysaccharide-igg-vaccine-responses-in-iga-deficient-mice
#4
Yoichi Furuya, Girish S Kirimanjeswara, Sean Roberts, Rachael Racine, Jennifer Wilson-Welder, Alan M Sanfilippo, Sharon L Salmon, Dennis W Metzger
We report that IgA(-/-) mice exhibit specific defects in IgG antibody responses to various polysaccharide vaccines (Francisella tularensis LPS and Pneumovax), but not protein vaccines such as Fluzone. This defect further included responses to polysaccharide-protein conjugate vaccines (Prevnar and Haemophilus influenzae type b-tetanus toxoid vaccine). In agreement with these findings, IgA(-/-) mice were protected from pathogen challenge with protein- but not polysaccharide-based vaccines. Interestingly, after immunization with live bacteria, IgA(+/+) and IgA(-/-) mice were both resistant to lethal challenge and their IgG anti-polysaccharide antibody responses were comparable...
July 31, 2017: Vaccine
https://www.readbyqxmd.com/read/28755524/structure-of-the-francisella-response-regulator-qseb-receiver-domain-and-characterization-of-qseb-inhibition-by-antibiofilm-2-aminoimidazole-based-compounds
#5
Morgan E Milton, C Leigh Allen, Erik A Feldmann, Benjamin G Bobay, David K Jung, Matthew D Stephens, Roberta J Melander, Kelly E Theisen, Daina Zeng, Richele J Thompson, Christian Melander, John Cavanagh
With antibiotic resistance increasing at alarming rates, targets for new antimicrobial therapies must be identified. A particularly promising target is the bacterial two-component system. Two-component systems allow bacteria to detect, evaluate and protect themselves against changes in the environment, such as exposure to antibiotics, and also to trigger production of virulence factors. Drugs that target the response regulator portion of two-component systems represent a potent new approach so far unexploited...
July 29, 2017: Molecular Microbiology
https://www.readbyqxmd.com/read/28754318/anion-inhibitors-of-the-%C3%AE-carbonic-anhydrase-from-the-pathogenic-bacterium-responsible-of-tularemia-francisella-tularensis
#6
Sonia Del Prete, Daniela Vullo, Sameh M Osman, Zeid AlOthman, William A Donald, Jean-Yves Winum, Claudiu T Supuran, Clemente Capasso
A β-class carbonic anhydrase (CA, EC 4.2.1.1) from the pathogenic bacterium Francisella tularensis (FtuβCA) was cloned and purified, and the anion inhibition profile was investigated. Based on the measured kinetic parameters for the enzyme catalyzed CO2 hydration reaction (kcat of 9.8×10(5)s(-1) and a kcat/KM of 8.9×10(7)M(-1)s(-1)), FtuβCA is a highly effective enzyme. The activity of FtuβCA was not inhibited by a range of anions that do not typically coordinate Zn(II) effectively, including perchlorate, tetrafluoroborate, and hexafluorophosphate...
July 17, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28750854/tularemia-vaccine-safety-reactogenicity-take-skin-reactions-and-antibody-responses-following-vaccination-with-a-new-lot-of-the-francisella-tularensis-live-vaccine-strain-a-phase-2-randomized-clinical-trial
#7
Mark J Mulligan, Jack T Stapleton, Wendy A Keitel, Sharon E Frey, Wilbur H Chen, Nadine Rouphael, Srilatha Edupuganti, Allison Beck, Patricia L Winokur, Hana M El Sahly, Shital M Patel, Robert L Atmar, Irene Graham, Edwin Anderson, Samer S El-Kamary, Marcela F Pasetti, Marcelo B Sztein, Heather Hill, Johannes B Goll
BACKGROUND: Tularemia is caused by Francisella tularensis, a gram-negative bacterium that has been weaponized as an aerosol. For protection of personnel conducting biodefense research, the United States Army required clinical evaluation of a new lot of tularemia live vaccine strain manufactured in accordance with Current Good Manufacturing Practices. METHODS: A phase 2 randomized clinical trial compared the new lot (DVC-LVS) to the existing vaccine that has been in use for decades (USAMRIID-LVS)...
July 24, 2017: Vaccine
https://www.readbyqxmd.com/read/28745813/subversion-of-innate-immune-responses-by-francisella-involves-the-disruption-of-traf3-and-traf6-signaling-complexes
#8
Daniela Putzova, Swarupa Panda, Anetta Härtlova, Jiří Stulík, Nelson O Gekara
The success of pathogens depends on their ability to circumvent immune defenses. Francisella tularensis is one of the most infectious bacteria known. The remarkable virulence of Francisella is believed to be due to its capacity to evade or subvert the immune system, but how remains obscure. Here we show that Francisella triggers but concomitantly inhibits the Toll-like receptor (TLR), RIG-I-like receptor (RLR) and Cytoplasmic DNA (CDR) pathways. Francisella subverts these pathways at least in part by inhibiting K63-linked polyubiquitination and assembly of TRAF6 and TRAF3 complexes that control the transcriptional responses of PRRs...
July 26, 2017: Cellular Microbiology
https://www.readbyqxmd.com/read/28745311/outer-membrane-vesicle-associated-lipase-ftla-enhances-cellular-invasion-and-virulence-in-francisella-tularensis-lvs
#9
Fei Chen, Guolin Cui, Shuxia Wang, Manoj Kumar Mohan Nair, Lihong He, Xinyi Qi, Xiangmin Han, Hanqi Zhang, Jing-Ren Zhang, Jingliang Su
Francisella tularensis is a highly infectious intracellular pathogen that infects a wide range of host species and causes fatal pneumonic tularemia in humans. ftlA was identified as a potential virulence determinant of the F. tularensis live vaccine strain (LVS) in our previous transposon screen, but its function remained undefined. Here, we show that an unmarked deletion mutant of ftlA was avirulent in a pneumonia mouse model with a severely impaired capacity to infect host cells. Consistent with its sequence homology with GDSL lipase/esterase family proteins, the FtlA protein displayed lipolytic activity in both E...
July 26, 2017: Emerging Microbes & Infections
https://www.readbyqxmd.com/read/28739830/complement-c3-as-a-prompt-for-human-macrophage-death-during-infection-with-francisella-tularensis-strain-schu-s4
#10
Susan R Brock, Michael J Parmely
Tularemia is caused by the gram-negative bacterial pathogen Francisella tularensis Infection of macrophages and their subsequent death are believed to play important roles in the progression of disease. Because complement is a particularly effective opsonin for Francisella, we asked whether complement-dependent uptake of F. tularensis strain SCHU S4 affects the survival of primary human macrophages during infection. Complement component C3 was found to be an essential opsonin in human serum not only for greatly increased uptake of SCHU S4, but for the induction of macrophage death...
July 24, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28739786/benzoxazoles-phthalazinones-and-arylurea-based-compounds-with-impdh-independent-antibacterial-activity-against-francisella-tularensis
#11
Suresh Kumar Gorla, Yan Zhang, Meaghan M Rabideau, Aiping Qin, Shibin Chacko, Amanda L House, Corey R Johnson, Kavitha Mandapati, Hannah M Bernstein, Elizabeth S McKenney, Helena Boshoff, Minjia Zhang, Ian J Glomski, Joanna B Goldberg, Gregory D Cuny, Barbara J Mann, Lizbeth Hedstrom
Francisella tularensis is the causative agent of tularemia and a potential biowarfare agent. The virulence of F. tularensis is decreased by deletion of guaB, the gene encoding inosine monophosphate dehydrogenase (IMPDH), suggesting that this enzyme is a target for antibacterial design. Here we report that F. tularensis growth is blocked by inhibitors of bacterial IMPDHs. Seventeen compounds from two different frameworks, designated D and Q, display antibacterial activity with minimum inhibitory concentrations less than 1 μM...
July 24, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28732514/in-vitro-assessment-of-the-antimicrobial-activity-of-silver-and-zinc-oxide-nanoparticles-against-fish-pathogens
#12
Mohamed Ibrahim Shaalan, Magdy Mohamed El-Mahdy, Sarah Theiner, Mansour El-Matbouli, Mona Saleh
BACKGROUND: Antibiotic resistance is a global issue that threatens public health. The excessive use of antibiotics contributes to this problem as the genes of antibiotic resistance can be transferred between the bacteria in humans, animals and aquatic organisms. Metallic nanoparticles could serve as future substitutes for some conventional antibiotics because of their antimicrobial activity. The aim of this study was to evaluate the antimicrobial effects of silver and zinc oxide nanoparticles against major fish pathogens and assess their safety in vitro...
July 21, 2017: Acta Veterinaria Scandinavica
https://www.readbyqxmd.com/read/28726608/density-dependent-prevalence-of-francisella-tularensis-in-fluctuating-vole-populations-northwestern-spain
#13
Ruth Rodríguez-Pastor, Raquel Escudero, Dolors Vidal, François Mougeot, Beatriz Arroyo, Xavier Lambin, Ave Maria Vila-Coro, Isabel Rodríguez-Moreno, Pedro Anda, Juan J Luque-Larena
Tularemia in humans in northwestern Spain is associated with increases in vole populations. Prevalence of infection with Francisella tularensis in common voles increased to 33% during a vole population fluctuation. This finding confirms that voles are spillover agents for zoonotic outbreaks. Ecologic interactions associated with tularemia prevention should be considered.
August 2017: Emerging Infectious Diseases
https://www.readbyqxmd.com/read/28725638/isolation-of-f-novicida-containing-phagosome-from-infected-human-monocyte-derived-macrophages
#14
Valentina Marecic, Olga Shevchuk, Mateja Ozanic, Mirna Mihelcic, Michael Steinert, Antonija Jurak Begonja, Yousef Abu Kwaik, Marina Santic
Francisella is a gram-negative bacterial pathogen, which causes tularemia in humans and animals. A crucial step of Francisella infection is its invasion of macrophage cells. Biogenesis of the Francisella-containing phagosome (FCP) is arrested for ~15 min at the endosomal stage, followed by gradual bacterial escape into the cytosol, where the microbe proliferates. The crucial step in pathogenesis of tularemia is short and transient presence of the bacterium within phagosome. Isolation of FCPs for further studies has been challenging due to the short period of time of bacterial residence in it and the characteristics of the FCP...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28721222/serological-evidence-of-francisella-tularensis-in-febrile-patients-seeking-treatment-at-remote-hospitals-northeastern-kenya-2014-2015
#15
J Njeru, H Tomaso, K Mertens, K Henning, G Wareth, R Heller, S Kariuki, E M Fèvre, H Neubauer, M W Pletz
Tularaemia is a highly contagious infectious zoonosis caused by the bacterial agent Francisella tularensis. The aim of this study was to investigate the presence of antibodies to F. tularensis in febrile patients in northeastern Kenya. During 2014-2015, 730 patients were screened for anti-F. tularensis antibodies using a combination of ELISA and Western blot. Twenty-seven (3.7%) individuals were positive for F. tularensis. Tularaemia was not suspected by the treating clinicians in any of them. Our results suggest that tularaemia may be present in Kenya but remain unreported, and emphasizes the need for local clinicians to broaden their diagnostic repertoire when evaluating patients with undifferentiated febrile illness...
September 2017: New Microbes and New Infections
https://www.readbyqxmd.com/read/28710265/francisella-like-endosymbionts-and-rickettsia-species-in-local-and-imported-hyalomma-ticks
#16
Tal Azagi, Eyal Klement, Gidon Perlman, Yaniv Lustig, Kosta Y Mumcuoglu, Dmitry Apanaskevich, Yuval Gottlieb
Hyalomma ticks (Acari: Ixodidae) are hosts for Francisella like endosymbionts (FLE) and may serve as vectors of zoonotic disease agents. This study was aimed to provide initial characterization of the interaction between Hyalomma and FLE and to determine the prevalence of pathogenic Rickettsia in these ticks. Hyalomma marginatum, H. rufipes, H. dromedarii, H. aegyptium and H. excavatum ticks, identified morphologically and molecularly, were collected from different hosts and locations, representing the genus distribution in Israel, as well as from migratory birds...
July 14, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28702010/comparison-among-the-quantification-of-bacterial-pathogens-by-qpcr-dpcr-and-cultural-methods
#17
Matteo Ricchi, Cristina Bertasio, Maria B Boniotti, Nadia Vicari, Simone Russo, Michela Tilola, Marco A Bellotti, Barbara Bertasi
The demand for rapid methods for the quantification of pathogens is increasing. Among these methods, those based on nucleic acids amplification (quantitative PCRs) are the most widespread worldwide. Together with the qPCR, a new approach named digital PCR (dPCR), has rapidly gained importance. The aim of our study was to compare the results obtained using two different dPCR systems and one qPCR in the quantification of three different bacterial pathogens: Listeria monocytogenes, Francisella tularensis, and Mycobacterium avium subsp...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28695850/assembly-of-francisella-novicida-cpf1-endonuclease-in-complex-with-guide-rna-and-target-dna
#18
Pablo Alcón, Guillermo Montoya, Stefano Stella
Bacteria and archaea use the CRISPR-Cas system as an adaptive response against infection by foreign nucleic acids. Owing to its remarkable flexibility, this mechanism has been harnessed and adopted as a powerful tool for genome editing. The CRISPR-Cas system includes two classes that are subdivided into six types and 19 subtypes according to conservation of the cas gene and loci organization. Recently, a new protein with endonuclease activity belonging to class 2 type V has been identified. This endonuclease, termed Cpf1, in complex with a single CRISPR RNA (crRNA) is able to recognize and cleave a target DNA preceded by a 5'-TTN-3' protospacer-adjacent motif (PAM) complementary to the RNA guide...
July 1, 2017: Acta Crystallographica. Section F, Structural Biology Communications
https://www.readbyqxmd.com/read/28690600/differential-growth-of-francisella-tularensis-which-alters-expression-of-virulence-factors-dominant-antigens-and-surface-carbohydrate-synthases-governs-the-apparent-virulence-of-ft-schus4-to-immunized-animals
#19
Kristen M Holland, Sarah J Rosa, Kolbrun Kristjansdottir, Donald Wolfgeher, Brian J Franz, Tiffany M Zarrella, Sudeep Kumar, Raju Sunagar, Anju Singh, Chandra S Bakshi, Prachi Namjoshi, Eileen M Barry, Timothy J Sellati, Stephen J Kron, Edmund J Gosselin, Douglas S Reed, Karsten R O Hazlett
The gram-negative bacterium Francisella tularensis (Ft) is both a potential biological weapon and a naturally occurring microbe that survives in arthropods, fresh water amoeba, and mammals with distinct phenotypes in various environments. Previously, we used a number of measurements to characterize Ft grown in Brain-Heart Infusion (BHI) broth as (1) more similar to infection-derived bacteria, and (2) slightly more virulent in naïve animals, compared to Ft grown in Mueller Hinton Broth (MHB). In these studies we observed that the free amino acids in MHB repress expression of select Ft virulence factors by an unknown mechanism...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28689870/in-vitro-and-in-vivo-evaluation-of-fluoroquinolone-resistance-associated-with-dna-gyrase-mutations-in-francisella-tularensis-including-in-tularaemia-patients-with-treatment-failure
#20
V Sutera, G Hoarau, P Renesto, Y Caspar, M Maurin
Fluoroquinolones (FQs) are highly effective for treating tularaemia, a zoonosis caused by Francisella tularensis, but failures and relapses remain common in patients with treatment delay or immunocompromised status. FQ-resistant strains of F. tularensis harboring mutations in the quinolone-resistance determining region (QRDR) of gyrA and gyrB, the genes encoding subunits A and B of DNA gyrase, have been selected in vitro. Such mutants have never been isolated from humans as this microorganism is difficult to culture...
July 6, 2017: International Journal of Antimicrobial Agents
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